Phillip E. Gander

Neural signatures of perceptual inference

Generative models, such as predictive coding, posit that perception results from a combination of sensory input and prior prediction, each weighted by its precision (inverse variance), with incongruence between these termed prediction error (deviation from prediction) or surprise (negative log probability of the sensory input). However, direct evidence for such a system, and the physiological basis of its computations, is lacking. Using an auditory stimulus whose pitch value changed according to specific rules, we controlled and separated the three key computational variables underlying perception, and discovered, using direct recordings from human auditory cortex, that surprise due to prediction violations is encoded by local field potential oscillations in the gamma band (>30 Hz), changes to predictions in the beta band (12-30 Hz), and that the precision of predictions appears to quantitatively relate to alpha band oscillations (8-12 Hz). These results confirm oscillatory codes for critical aspects of generative models of perception. DOI: http://dx.doi.org/10.7554/eLife.11476.001

A Brain System for Auditory Working Memory

The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. SIGNIFICANCE STATEMENT In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance.

Intracranial Mapping of a Cortical Tinnitus System using Residual Inhibition

Summary Tinnitus can occur when damage to the peripheral auditory system leads to spontaneous brain activity that is interpreted as sound [1, 2]. Many abnormalities of brain activity are associated with tinnitus, but it is unclear how these relate to the phantom sound itself, as opposed to predisposing factors or secondary consequences [3]. Demonstrating “core” tinnitus correlates (processes that are both necessary and sufficient for tinnitus perception) requires high-precision recordings of neural activity combined with a behavioral paradigm in which the perception of tinnitus is manipulated and accurately reported by the subject. This has been previously impossible in animal and human research. Here we present extensive intracranial recordings from an awake, behaving tinnitus patient during short-term modifications in perceived tinnitus loudness after acoustic stimulation (residual inhibition) [4], permitting robust characterization of core tinnitus processes. As anticipated, we observed tinnitus-linked low-frequency (delta) oscillations [5–9], thought to be triggered by low-frequency bursting in the thalamus [10, 11]. Contrary to expectation, these delta changes extended far beyond circumscribed auditory cortical regions to encompass almost all of auditory cortex, plus large parts of temporal, parietal, sensorimotor, and limbic cortex. In discrete auditory, parahippocampal, and inferior parietal “hub” regions [12], these delta oscillations interacted with middle-frequency (alpha) and high-frequency (beta and gamma) activity, resulting in a coherent system of tightly coupled oscillations associated with high-level functions including memory and perception.

The Brain Basis for Misophonia

Summary Misophonia is an affective sound-processing disorder characterized by the experience of strong negative emotions (anger and anxiety) in response to everyday sounds, such as those generated by other people eating, drinking, chewing, and breathing [1, 2, 3, 4, 5, 6, 7, 8]. The commonplace nature of these sounds (often referred to as “trigger sounds”) makes misophonia a devastating disorder for sufferers and their families, and yet nothing is known about the underlying mechanism. Using functional and structural MRI coupled with physiological measurements, we demonstrate that misophonic subjects show specific trigger-sound-related responses in brain and body. Specifically, fMRI showed that in misophonic subjects, trigger sounds elicit greatly exaggerated blood-oxygen-level-dependent (BOLD) responses in the anterior insular cortex (AIC), a core hub of the “salience network” that is critical for perception of interoceptive signals and emotion processing. Trigger sounds in misophonics were associated with abnormal functional connectivity between AIC and a network of regions responsible for the processing and regulation of emotions, including ventromedial prefrontal cortex (vmPFC), posteromedial cortex (PMC), hippocampus, and amygdala. Trigger sounds elicited heightened heart rate (HR) and galvanic skin response (GSR) in misophonic subjects, which were mediated by AIC activity. Questionnaire analysis showed that misophonic subjects perceived their bodies differently: they scored higher on interoceptive sensibility than controls, consistent with abnormal functioning of AIC. Finally, brain structural measurements implied greater myelination within vmPFC in misophonic individuals. Overall, our results show that misophonia is a disorder in which abnormal salience is attributed to particular sounds based on the abnormal activation and functional connectivity of AIC.

Sequence learning modulates neural responses and oscillatory coupling in human and monkey auditory cortex

Learning complex ordering relationships between sensory events in a sequence is fundamental for animal perception and human communication. While it is known that rhythmic sensory events can entrain brain oscillations at different frequencies, how learning and prior experience with sequencing relationships affect neocortical oscillations and neuronal responses is poorly understood. We used an implicit sequence learning paradigm (an “artificial grammar”) in which humans and monkeys were exposed to sequences of nonsense words with regularities in the ordering relationships between the words. We then recorded neural responses directly from the auditory cortex in both species in response to novel legal sequences or ones violating specific ordering relationships. Neural oscillations in both monkeys and humans in response to the nonsense word sequences show strikingly similar hierarchically nested low-frequency phase and high-gamma amplitude coupling, establishing this form of oscillatory coupling—previously associated with speech processing in the human auditory cortex—as an evolutionarily conserved biological process. Moreover, learned ordering relationships modulate the observed form of neural oscillatory coupling in both species, with temporally distinct neural oscillatory effects that appear to coordinate neuronal responses in the monkeys. This study identifies the conserved auditory cortical neural signatures involved in monitoring learned sequencing operations, evident as modulations of transient coupling and neuronal responses to temporally structured sensory input.

An Integrative Tinnitus Model Based on Sensory Precision

Tinnitus is a common disorder that often complicates hearing loss. Its mechanisms are incompletely understood. Current theories proposing pathophysiology from the ear to the cortex cannot individually – or collectively – explain the range of experimental evidence available. We propose a new framework, based on predictive coding, in which spontaneous activity in the subcortical auditory pathway constitutes a ‘tinnitus precursor’ which is normally ignored as imprecise evidence against the prevailing percept of ‘silence’. Extant models feature as contributory mechanisms acting to increase either the intensity of the precursor or its precision. If precision (i.e., postsynaptic gain) rises sufficiently then tinnitus is perceived. Perpetuation arises through focused attention, which further increases the precision of the precursor, and resetting of the default prediction to expect tinnitus.

The demodulated band transform.

BACKGROUND Windowed Fourier decompositions (WFD) are widely used in measuring stationary and non-stationary spectral phenomena and in describing pairwise relationships among multiple signals. Although a variety of WFDs see frequent application in electrophysiological research, including the short-time Fourier transform, continuous wavelets, bandpass filtering and multitaper-based approaches, each carries certain drawbacks related to computational efficiency and spectral leakage. This work surveys the advantages of a WFD not previously applied in electrophysiological settings. NEW METHODS A computationally efficient form of complex demodulation, the demodulated band transform (DBT), is described. RESULTS DBT is shown to provide an efficient approach to spectral estimation with minimal susceptibility to spectral leakage. In addition, it lends itself well to adaptive filtering of non-stationary narrowband noise. COMPARISON WITH EXISTING METHODS A detailed comparison with alternative WFDs is offered, with an emphasis on the relationship between DBT and Thomsons multitaper. DBT is shown to perform favorably in combining computational efficiency with minimal introduction of spectral leakage. CONCLUSION DBT is ideally suited to efficient estimation of both stationary and non-stationary spectral and cross-spectral statistics with minimal susceptibility to spectral leakage. These qualities are broadly desirable in many settings.

Neural phase locking predicts BOLD response in human auditory cortex

ABSTRACT Natural environments elicit both phase‐locked and non‐phase‐locked neural responses to the stimulus in the brain. The interpretation of the BOLD signal to date has been based on an association of the non‐phase‐locked power of high‐frequency local field potentials (LFPs), or the related spiking activity in single neurons or groups of neurons. Previous studies have not examined the prediction of the BOLD signal by phase‐locked responses. We examined the relationship between the BOLD response and LFPs in the same nine human subjects from multiple corresponding points in the auditory cortex, using amplitude modulated pure tone stimuli of a duration to allow an analysis of phase locking of the sustained time period without contamination from the onset response. The results demonstrate that both phase locking at the modulation frequency and its harmonics, and the oscillatory power in gamma/high‐gamma bands are required to predict the BOLD response. Biophysical models of BOLD signal generation in auditory cortex therefore require revision and the incorporation of both phase locking to rhythmic sensory stimuli and power changes in the ensemble neural activity.

Tinnitus Suppression in Cochlear Implant Patients Using a Sound Therapy App

Purpose The use of acoustic stimuli to reduce the prominence of tinnitus has been used for decades. Counseling and tinnitus sound therapy options are not currently widespread for cochlear implant (CI) users. The goal of this study was to determine whether tinnitus therapy sounds created for individuals with acoustic hearing may also benefit CI users. Method Sixteen sounds from the ReSound Relief app (Version 3.0) were selected for the study. Sixteen participants were asked to rate the overall acceptability of each sound and to write the description of the sound they perceived. Sounds were streamed from an Apple™ iPod (6th generation) to the CI using a Cochlear™ Wireless Mini Microphone 2+. Thirteen participants then completed a 5-min trial where they rated their pretrial and posttrial tinnitus and the acceptability of a subset of preferred sounds. Ten out of these 13 participants completed a 2-week home trial with a preferred sound after which they answered an online tinnitus questionnaire and rated the effectiveness of the sound therapy. Results Individual differences were large. Results from the 5-min trial showed that sounds perceived as rain, music, and waves were rated the most acceptable. For all of the participants, the posttrial tinnitus loudness rating was lower than the pretrial rating, with some participants experiencing greater difference in their tinnitus loudness than others. At the end of the 2-week home trial, 3 of 10 participants rated the effectiveness of sound therapy 70% or higher. Conclusion The results suggest that the use of tinnitus therapy sounds delivered through a CI can be acceptable and provides relief for some tinnitus sufferers.